Hypersensitivity of ataxia telangiectasia skin fibroblasts to DNA alkylating agents.
3 ataxia telangiectasia (AT) fibroblast cell strains, AT4BI, AT5BI and AT2BE (CRL1343) were studied for their colony-forming ability after treatment with various concentrations of 4 different DNA alkylating agents. The results were compared to the response of fibroblast strains from 3 normal individuals. None of the AT strains were abnormally sensitive to N-methyl-N'-nitro-N-nitrosoguanidine. 1 strain (AT5BI) was significantly more sensitive to treatment with methyl methanesulfonate (MMS) based on a survival curve D0 value of 0.29 mM vs. the normal average D0 of 0.38 mM (P less than 0.02) and a D10 value of 0.85 mM vs. the normal average D10 of 1.2 mM (P less than 0.025). Strain AT4BI was also significantly more sensitive to MMS treatment when D10 values were compared (0.73 mM, P less than 0.01). All 3 AT cell strains were significantly more sensitive to treatment with ethyl methanesulfonate when D10 values were the criterion of sensitivity, AT4BI 16 mM, AT5BI 13 mM and AT2BE 15 mM vs. the normal human fibroblast average D10 value of 28 mM (P less than 0.01 for all 3 AT strains). 2 of the 3 AT cell strains (AT4BI and AT2BE) were abnormally sensitive to treatment with 4-nitroquinoline-1-oxide; the D0 values were 0.045 microM and 0.05 microM, respectively, vs. the normal average D0 value of 0.11 microM (P less than 0.01 for both AT strains). The corresponding D10 values were 0.08 microM and 0.11 microM, respectively, vs. the normal average D10 value of 0.27 microM (P less than 0.01 for AT4BI and P less than 0.025 for AT2BE). These results indicate that there is a heterogeneity in the response of AT fibroblast cell strains to treatment with DNA alkylating agents, except possibly in the case of ethylating compounds.
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D000477:Alkylating Agents / Q000494:pharmacology*; D001260:Ataxia Telangiectasia / Q000503:physiopathology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D012016:Reference Values; D012867:Skin / Q000503:physiopathology*
D000477:Alkylating Agents; D008769:Methylnitronitrosoguanidine; D015112:4-Nitroquinoline-1-oxide; D005020:Ethyl Methanesulfonate; D008741:Methyl Methanesulfonate